Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced...

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Veröffentlicht in:	PloS one 2012-11, Vol.7 (11), p.e49524
Hauptverfasser:	van Swelm, Rachel P L, Laarakkers, Coby M M, van der Kuur, Ellen C, Morava-Kozicz, Eva, Wevers, Ron A, Augustijn, Kevin D, Touw, Daan J, Sandel, Maro H, Masereeuw, Rosalinde, Russel, Frans G M
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetaminophen Acetaminophen - adverse effects Acetaminophen - pharmacology Adolescent Adult Aged Alanine Alanine transaminase Analgesics Animals Biological markers Biology Biomarkers Biomarkers - urine Calcium-binding protein Calmodulin Calmodulin - urine Carbonic anhydrase Carbonic anhydrases Carbonic Anhydrases - urine Chemical and Drug Induced Liver Injury - diagnosis Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - urine Dose-Response Relationship, Drug Enzymes Female Homeostasis Humans Injuries Intoxication Laboratory animals Liver Liver diseases Male Medical research Medicine Metabolism Metabolites Mice Middle Aged Oxidative stress Patients Pediatrics Pharmacology Plasma Profiling Proteins Proteome Proteomics Rodents Superoxide dismutase Superoxide Dismutase - urine Superoxide Dismutase-1 Superoxides Toxicology Translation Urine Young Adult
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Zusammenfassung:	Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (p
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0049524